As is well-known, viruses are the etiologic cause of many, sometimes life-threatening, diseases of both humans and animals. For example, herpes viruses such as herpes simplex 1 (HSV-1), herpes simplex 2 (HSV-2), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zoster virus (VZV) and human herpes virus 6 (HHV 6) are associated with many common viral illnesses.
Human CMV (HCMV) infection is a life-long affliction which can result in morbidity and mortality. The pathologies associated with HMCV include microcephaly, heptosplenomegaly, jaundice, encephalitis, infections of the newborn infants or fetuses in utero, and infections of immunocompromised hosts.
For several reasons, increasing numbers of persons are at risk for HCMV infection, and presently an estimated 80% of adults in the United States are infected with HCMV. A particularly susceptible group is those of weakened immune system, such as AIDS patients, where HCMV infection may cause retinitis, gastritis and pneumonitis. Also, HCMV-induced pneumonias or hepatitis are frequent and serious complications of bone marrow transplants.
European patent EP 0 238 459 relates to substituted indoloquinoxalines having the general formula
wherein R1 represents hydrogen or one or several, preferably 1 to 4, similar or different substituents in the positions 1-4 and/or 7-10, selected from halogen, preferably Br, lower alkyl/alkoxy group having not more than 4 carbon atoms, trifluoromethyl group, trichloromethyl group; X is a group —(CH2)n—R2, wherein R2 represents a nitrogen containing basic residue such as NH2, NHR4 or NR5R6, wherein R4, R5 and R6 independently are lower alkyl or cycloalkyl and n is an integer of from 1 to 4 and R3 represents hydrogen, lower alkyl/cycloalkyl group having not more than 4 carbon atoms, and the physiologically acceptable addition products of the compounds with acids and halogen adducts, preferably adducts with iodine, iodine monochloride or iodine monobromide.
However, it is clear that there still exists an urgent need for new medicaments having antiviral efficacy, in particular against herpes viruses such as HMCV, and an object of the present invention is to provide compounds fulfilling this need.